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2. Molnupiravir versus placebo in unvaccinated and vaccinated patients with early SARS-CoV-2 infection in the UK (AGILE CST-2): a randomised, placebo-controlled, double-blind, phase 2 trial

Author

Paton, Nicholas, Hayden, Fred, Darbyshire, Janet, Lucas, Amy, Lorch, Ulrika, Freedman, Andrew, Knight, Richard, Julious, Stevan, Byrne, Rachel, Cubas Atienzar, Ana, Jones, Jayne, Williams, Chris, Song, Anna, Dixon, Jan, Alexandersson, Anja, Hatchard, Parys, Tilt, Emma, Titman, Andrew, Doce Carracedo, Ale, Chandran Gorner, Vatsi, Davies, Andrea, Woodhouse, Louis, Carlucci, Nicola, Okenyi, Emmanuel, Bula, Marcin, Dodd, Kate, Gibney, Jennifer, Dry, Lesley, Rashid Gardner, Zalina, Sammour, Amin, Cole, Christine, Rowland, Tim, Tsakiroglu, Maria, Yip, Vincent, Osanlou, Rostam, Stewart, Anna, Parker, Ben, Turgut, Tolga, Ahmed, Afshan, Starkey, Kay, Subin, Sujamole, Stockdale, Jennifer, Herring, Lisa, Baker, Jonathon, Oliver, Abigail, Pacurar, Mihaela, Owens, Dan, Munro, Alistair, Babbage, Gavin, Faust, Saul, Harvey, Matthew, Pratt, Danny, Nagra, Deepak, Vyas, Aashish, Khoo, Saye H, FitzGerald, Richard, Saunders, Geoffrey, Middleton, Calley, Ahmad, Shazaad, Edwards, Christopher J, Hadjiyiannakis, Dennis, Walker, Lauren, Lyon, Rebecca, Shaw, Victoria, Mozgunov, Pavel, Periselneris, Jimstan, Woods, Christie, Bullock, Katie, Hale, Colin, Reynolds, Helen, Downs, Nichola, Ewings, Sean, Buadi, Amanda, Cameron, David, Edwards, Thomas, Knox, Emma, Donovan-Banfield, I'ah, Greenhalf, William, Chiong, Justin, Lavelle-Langham, Lara, Jacobs, Michael, Northey, Josh, Painter, Wendy, Holman, Wayne, Lalloo, David G, Tetlow, Michelle, Hiscox, Julian A, Jaki, Thomas, Fletcher, Thomas, and Griffiths, Gareth

Published
2023
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4. Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Author

Munro, Alasdair P S, Feng, Shuo, Janani, Leila, Cornelius, Victoria, Aley, Parvinder K, Babbage, Gavin, Baxter, David, Bula, Marcin, Cathie, Katrina, Chatterjee, Krishna, Dodd, Kate, Enever, Yvanne, Qureshi, Ehsaan, Goodman, Anna L, Green, Christopher A, Harndahl, Linda, Haughney, John, Hicks, Alexander, van der Klaauw, Agatha A, Kanji, Nasir, Libri, Vincenzo, Llewelyn, Martin J, McGregor, Alastair C, Minassian, Angela M, Moore, Patrick, Mughal, Mehmood, Mujadidi, Yama F, Holliday, Kyra, Osanlou, Orod, Osanlou, Rostam, Owens, Daniel R, Pacurar, Mihaela, Palfreeman, Adrian, Pan, Daniel, Rampling, Tommy, Regan, Karen, Saich, Stephen, Bawa, Tanveer, Saralaya, Dinesh, Sharma, Sunil, Sheridan, Ray, Maallah, Mina, Thomson, Emma C, Todd, Shirley, Twelves, Chris, Read, Robert C, Charlton, Sue, Hallis, Bassam, Ramsay, Mary, Andrews, Nick, Lambe, Teresa, Nguyen-Van-Tam, Jonathan S, Snape, Matthew D, Liu, Xinxue, Faust, Saul N, Riordan, Andrew, Ustianowski, Andrew, Rogers, Chris, Katechia, Kashyap, Cooper, Alison, Freedman, Andrew, Hughes, Rachel, Grundy, Lynne, Tudor Jones, Lona, Harrison, Elizabeth, Snashall, Emma, Mallon, Lewis, Burton, Katharine, Storton, Kim, Munusamy, Malathi, Tandy, Bridget, Egbo, Akamino, Cox, Stephen, Ahmed, Nabeela Nazir, Shenoy, Anil, Bousfield, Rachel, Wixted, Donna, Gutteridge, Helen, Mansfield, Becky, Herbert, Christopher, Murira, Jennifer, Calderwood, James, Barker, Dominique, Brandon, Jacqueline, Tulloch, Hayley, Colquhoun, Suzie, Thorp, Helen, Radford, Helen, Evans, Julie, Baker, Helena, Thorpe, Jeanette, Batham, Sally, Hailstone, Jessica, Phillips, Rachael, Kumar, Dileep, Westwell, Fran, Sturdy, Ann, Barcella, Lara, Soussi, Najwa, Mpelembue, Mushiya, Raj, Sreena, Sharma, Rajni, Corrah, Tumena, John, Laurence, Whittington, Ashley, Roche, Siobhan, Wagstaff, Lynda, Farrier, Adam, Bisnauthsing, Karen, Abeywickrama, Movin, Spence, Niamh, Packham, Alice, Serafimova, Teona, Aslam, Suahil, McGreevy, Caitlin, Borca, Alessandro, DeLosSantosDominguez, Pamela, Palmer, Emily, Broadhead, Samantha, Farooqi, Sadaf, Piper, Jo, Weighell, Rowena, Pickup, Lorinda, Shamtally, Djamila, Domingo, Jason, Kourampa, Evgenia, Hale, Colin, Gibney, Jennifer, Stackpoole, Michael, Rashid-Gardner, Zalina, Lyon, Rebecca, McDonnell, Chloe, Cole, Christine, Stewart, Anna, McMillan, Gillian, Savage, Mary, Beckett, Helen, Moorbey, Chantelle, Desai, Amisha, Brown, Claire, Naker, Kush, Gokani, Karishma, Trinham, Charlotte, Sabine, Charlette, Moore, Sophie, Hurdover, Steve, Justice, Edwin, Stone, Megan, Plested, Emma, Ferreira Da Silva, Carla, White, Rachel, Robinson, Hannah, Turnbull, Iain, Morshead, Gertraud, Drake-Brockman, Rachael, Smith, Catherine, Li, Grace, Kasanyinga, Mwila, Clutterbuck, Elizabeth A, Bibi, Sagida, Singh, Michael, Champaneri, Trishna, Irwin, Margaret, Khan, Mohammed, Kownacka, Alicia, Nabunjo, Martha, Osuji, Carol, Hladkiwskyj, John, Galvin, Dominic, Patel, Gita, Grierson, Jacques, Males, Samantha, Askoolam, Krishna, Barry, Joshua, Mouland, Johanna, Longhurst, Beverley, Moon, Maria, Giddins, Beth, Pereira Dias Alves, Carlota, Richmond, Leah, Minnis, Christine, Baryschpolec, Sonia, Elliott, Scott, Fox, Lauren, Graham, Victoria, Baker, Natalie, Godwin, Kerry, Buttigieg, Karen, Knight, Chanice, Brown, Phillip, Lall, Paminder, Shaik, Imam, Chiplin, Emily, Brunt, Emily, Leung, Stephanie, Allen, Lauren, Thomas, Steve, Fraser, Sara, Choi, Bea, Gouriet, Jade, Perkins, Jonathan, Gowland, Andrew, Macdonald, Jonathan, Seenan, John Paul, Starinskij, Igor, Seaton, Andrew, Peters, Erica, Singh, Stephen, Gardside, Ben, Bonnaud, Avril, Davies, Ceri, Gordon, Elizabeth, Keenan, Samantha, Hall, Jane, Wilkins, Suzanne, Tasker, Suzanne, James, Rob, Seath, Ingrid, Littlewood, Kelly, Newman, Joseph, Boubriak, Iryna, Suggitt, Debbie, Haydock, Helen, Bennett, Sara, Woodyatt, Wiesia, Hughes, Kerry, Bell, Judith, Coughlan, Tricia, van Welsenes, Donald, Kamal, Mohammed, Cooper, Chris, Tunstall, Simon, Ronan, Nicholas, Cutts, Rebecca, Dare, Tracey, Yim, Yee Ting Nicole, Whittley, Sarah, Hamal, Shama, Ricamara, Marivic, Adams, Kirsty, Baker, Holly, Driver, Kimberley, Turner, Nicola, Rawlins, Todd, Roy, Subarna, Merida-Morillas, Marta, Sakagami, Yukari, Andrews, Antonette, Goncalvescordeiro, Lillian, Stokes, Matthew, Ambihapathy, Wythehi, Spencer, Joanne, Parungao, Nina, Berry, Lisa, Cullinane, James, Presland, Laura, Ross Russell, Amy, Warren, Sarah, Baker, Jonathan, Oliver, Abigail, Buadi, Amanda, Lee, Kim, Haskell, Louise, Romani, Rossana, Bentley, Ian, Whitbred, Tim, Fowler, Simon, Gavin, John, Magee, Alan, Watson, Tara, Nightingale, Kari, Marius, Phedra, Summerton, Eloise, Locke, Emily, Honey, Thomas, Lingwood, Aidan, de la Haye, Anastasia, Elliott, Ryan Stephen, Underwood, Karen, King, Mikayala, Davies-Dear, Sharon, Horsfall, Emily, Chalwin, Olivia, Burton, Holly, Edwards, Christopher J, Welham, Benjamin, Appleby, Kim, Dineen, Emily, Garrahy, Sarah, Hall, Fran, Ladikou, Eleni, Mullan, Dee, Hansen, Daniel, Campbell, Marion, Dos Santos, Filipa, Lakeman, Nicki, Branney, Debbie, Vamplew, Luke, Hogan, Alison, Frankham, Jorden, Wiselka, Martin, Vail, Denny, Wenn, Victoria, Renals, Valerie, Ellis, Kate, Lewis-Taylor, Jessica, Habash-Bailey, Haniah, Magan, Javier, and Hardy, Anna

Published
2022
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5. Are the Kids Alright? Exploring Students' Experiences of Support Mechanisms to Enhance Wellbeing on an Engineering Programme in the UK

Author

Chadha, Deesha, Kogelbauer, Andreas, Campbell, James, Hellgardt, Klaus, Maraj, Marsha, Shah, Umang, Brechtelsbauer, Clemens, and Hale, Colin

Abstract

In this paper, we aim to explore students' experiences of support mechanisms that support their wellbeing on an engineering degree programme at a research-intensive higher education institution and understand how theory relates to practice. This study was conducted using a mixed-methods approach involving student survey responses (N = 173), interviews with 16 students and focus groups. Kahu and Nelson's conceptual framework was used as a lens through which to explore student support mechanisms. Preliminary data analysis indicates that the intense workload adversely affects students as do some of the interactions they have with personal tutors and their peers. Our findings suggest that workload needs to be reduced, personal tutors need to fill gaps in their skills set, especially associated with student support, and institutional and departmental protocols be continually updated to support student wellbeing. Additionally, student wellbeing officers and professional, dedicated wellbeing advisors could be part of a long-term solution.

Published
2021
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6. Characterisation of SARS-CoV-2 genomic variation in response to molnupiravir treatment in the AGILE Phase IIa clinical trial

Author

Donovan-Banfield, I’ah, Penrice-Randal, Rebekah, Goldswain, Hannah, Rzeszutek, Aleksandra M., Pilgrim, Jack, Bullock, Katie, Saunders, Geoffrey, Northey, Josh, Dong, Xiaofeng, Ryan, Yan, Reynolds, Helen, Tetlow, Michelle, Walker, Lauren E., FitzGerald, Richard, Hale, Colin, Lyon, Rebecca, Woods, Christie, Ahmad, Shazaad, Hadjiyiannakis, Dennis, Periselneris, Jimstan, Knox, Emma, Middleton, Calley, Lavelle-Langham, Lara, Shaw, Victoria, Greenhalf, William, Edwards, Thomas, Lalloo, David G., Edwards, Christopher J., Darby, Alistair C., Carroll, Miles W., Griffiths, Gareth, Khoo, Saye H., Hiscox, Julian A., and Fletcher, Thomas

Published
2022
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8. Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial

Author

Riordan, Andrew, Ustianowski, Andrew, Rogers, Chris A, Hughes, Stephen, Longshaw, Laura, Stockport, Jane, Hughes, Rachel, Grundy, Lynne, Tudor Jones, Lona, Guha, Arpan, Snashall, Emma, Eadsforth, Tom, Reeder, Sally, Storton, Kim, Munusamy, Malathi, Tandy, Bridget, Egbo, Akamino, Cox, Stephen, Ahmed, Nabeela Nazir, Shenoy, Anil, Bousfield, Rachel, Wixted, Donna, Gutteridge, Helen, Mansfield, Becky, Herbert, Christopher, Holliday, Kyra, Calderwood, James, Barker, Dominique, Brandon, Jacqueline, Tulloch, Hayley, Colquhoun, Suzie, Thorp, Helen, Radford, Helen, Evans, Julie, Baker, Helena, Thorpe, Jeanette, Batham, Sally, Hailstone, Jessica, Phillips, Rachael, Kumar, Dileep, Westwell, Fran, Makia, Fiona, Hopkins, NinaSimone, Barcella, Lara, Mpelembue, Mushiya, dabagh, Maja, lang, Matilda, khan, Farida, Adebambo, Olumide, Chita, Sunder, Corrah, Tumena, Whittington, Ashley, John, Laurence, Roche, Siobhan, Wagstaff, Lynda, Farrier, Adam, Bisnauthsing, Karen, Serafimova, Teona, Nanino, Elisa, Cooney, Enya, Wilson-Goldsmith, Jaimie, Nguyen, Hanna, Mazzella, Andrea, Jackson, Beth, Aslam, Suahil, Bawa, Tanveer, Broadhead, Samantha, Farooqi, Sadaf, Piper, Jo, Weighell, Rowena, Pickup, Lorinda, Shamtally, Djamila, Domingo, Jason, Kourampa, Evgenia, Hale, Colin, Gibney, Jennifer, Stackpoole, Michael, Rashid-Gardner, Zalina, Lyon, Rebecca, McDonnell, Chloe, Cole, Christine, Stewart, Anna, McMillan, Gillian, Savage, Mary, Beckett, Helen, Moorbey, Chantelle, Desai, Amisha, Brown, Claire, Naker, Kush, Qureshi, Ehsaan, Trinham, Charlotte, Sabine, Charlotte, Moore, Sophie, Hurdover, Steve, Justice, Edwin, Smith, David, Plested, Emma, Ferreira Da Silva, Carla, White, Rachel, Robinson, Hannah, Cifuentes, Liliana, Morshead, Gertraud, Drake-Brockman, Rachael, Kinch, Patrick, Kasanyinga, Mwila, Clutterbuck, Elizabeth A., Bibi, Sagida, Stuart, Arabella SV, Shaw, Robert H, Singh, Michael, Champaneri, Trishna, Irwin, Margaret, Khan, Mohammed, Kownacka, Alicja, Nabunjo, Martha, Osuji, Carool, Hladkiwskyj, John, Galvin, Dominic, Patel, Gita, Mouland, Johanna, Longhurst, Beverley, Moon, Maria, Giddins, Beth, Pereira Dias Alves, Carlota, Richmond, Leah, Minnis, Christine, Baryschpolec, Sonia, Elliott, Scott, Fox, Lauren, Graham, Victoria, Baker, Natalie, Godwin, Kerry, Buttigieg, Karren, Knight, Chanice, Brown, Phillip, Lall, Paminder, Shaik, Imam, Chiplin, Emily, Brunt, Emily, Leung, Stephanie, Allen, Lauren, Thomas, Steve, Fraser, Sara, Choi, Bea, Gouriet, Jade, Freedman, Andrew, Perkins, Jonathan, Gowland, Andrew, Macdonald, Jonathan, Seenan, John Paul, Starinskij, Igor, Seaton, Andrew, Peters, Erica, Singh, Stephen, Gardside, Ben, Bonnaud, Avril, Davies, Ceri, Gordon, Elizabeth, Keenan, Samantha, Hall, Jane, Wilkins, Suzanne, Tasker, Suzanne, James, Rob, Seath, Ingrid, Littlewood, Kelly, Newman, Joseph, Boubriak, Iryna, Suggitt, Debbie, Haydock, Helen, Bennett, Sara, Woodyatt, Wiesia, Hughes, Kerry, Bell, Judith, Coughlan, Tricia, van Welsenes, Donald, Kamal, Mohammed, Cooper, Chris, Tunstall, Simon, Ronan, Nicholas, Cutts, Rebecca, Dare, Tracey, Yim, Yee Ting Nicole, Whittley, Sarah, Ricamara, Marivic, Hamal, Shama, Adams, Kirsty, Baker, Holly, Driver, Kimberley, Turner, Nicola, Rawlins, Todd, Roy, Subarna, Merida-Morillas, Marta, Sakagami, Yukari, Andrews, Antonette, Goncalves cordeiro, Lillian, Stokes, Matthew, Ambihapathy, Wythehi, Spencer, Joanne, Parungao, Nina, Berry, Lisa, Cullinane, James, Presland, Laura, Ross-Russell, Amy, Warren, Sarah, Baker, Jonathan, Oliver, Abigail, Buadi, Amanda, Lee, Kim, Haskell, Louise, Romani, Rossana, Bentley, Ian, Whitbred, Tim, Fowler, Simon, Gavin, John, Magee, Alan, Watson, Tara, Nightingale, Kari, Marius, Phedra, Summerton, Eloise, Locke, Emily, Honey, Thomas, Lingwood, Aidan, de la Haye, Anastasia, Elliott, Ryan Stephen, Underwood, Karen, King, Mikayala, Davies-Dear, Sharon, Horsfall, Emily, Chalwin, Olivia, Burton, Holly, Edwards, Christopher J, Welham, Benjamin, Garrahy, Sarah, Hall, Fran, Ladikou, Eleni, Mullan, Dee, Hansen, Daniel, Campbell, Marion, Dos Santos, Filipa, Habash-Bailey, Haniah, Lakeman, Nicki, Branney, Debbie, Vamplew, Luke, Hogan, Alison, Frankham, Jorden, Wiselka, Martin, Vail, Dennyl, Wenn, Victoria, Renals, Valerie, Ellis, Kate, Lewis-Taylor, Jessica, Magan, Javier, Hardy, Anna, Appleby, Kim, Munro, Alasdair P S, Janani, Leila, Cornelius, Victoria, Aley, Parvinder K, Babbage, Gavin, Baxter, David, Bula, Marcin, Cathie, Katrina, Chatterjee, Krishna, Dodd, Kate, Enever, Yvanne, Gokani, Karishma, Goodman, Anna L, Green, Christopher A, Harndahl, Linda, Haughney, John, Hicks, Alexander, van der Klaauw, Agatha A, Kwok, Jonathan, Lambe, Teresa, Libri, Vincenzo, Llewelyn, Martin J, McGregor, Alastair C, Minassian, Angela M, Moore, Patrick, Mughal, Mehmood, Mujadidi, Yama F, Murira, Jennifer, Osanlou, Orod, Osanlou, Rostam, Owens, Daniel R, Pacurar, Mihaela, Palfreeman, Adrian, Pan, Daniel, Rampling, Tommy, Regan, Karen, Saich, Stephen, Salkeld, Jo, Saralaya, Dinesh, Sharma, Sunil, Sheridan, Ray, Sturdy, Ann, Thomson, Emma C, Todd, Shirley, Twelves, Chris, Read, Robert C, Charlton, Sue, Hallis, Bassam, Ramsay, Mary, Andrews, Nick, Nguyen-Van-Tam, Jonathan S, Snape, Matthew D, Liu, Xinxue, and Faust, Saul N

Published
2021
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18. Pharmacokinetics of ß-d-N4-Hydroxycytidine, the Parent Nucleoside of Prodrug Molnupiravir, in Nonplasma Compartments of Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Author

FitzGerald, Richard, Dickinson, Laura, Else, Laura, Fletcher, Thomas, Hale, Colin, Amara, Alieu, Walker, Lauren, Penchala, Sujan Dilly, Lyon, Rebecca, Shaw, Victoria, Greenhalf, William, Bullock, Katie, Lavelle-Langham, Lara, Reynolds, Helen, Painter, Wendy, Holman, Wayne, Ewings, Sean, Griffiths, Gareth, and Khoo, Saye

Subjects
SALIVA analysis, COVID-19, PRODRUGS, NUCLEOSIDES, ANTIVIRAL agents, TEARS (Body fluid)
Abstract

ß-d-N4-hydroxycytidine (NHC), the parent nucleoside of molnupiravir, a COVID-19 antiviral, was quantified at SARS-CoV-2 transmission sites in 12 patients enrolled in AGILE Candidate-Specific Trial-2. Saliva, nasal, and tear NHC concentrations were 3%, 21%, and 22% that of plasma. Saliva and nasal NHC were significantly correlated with plasma (P  < .0001). Clinical Trials Registration. NCT04746183. [ABSTRACT FROM AUTHOR]

Published
2022
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20. An Open Label, Adaptive, Phase 1 Trial of High‐Dose Oral Nitazoxanide in Healthy Volunteers: An Antiviral Candidate for SARS‐CoV‐2.

Author

Walker, Lauren E., FitzGerald, Richard, Saunders, Geoffrey, Lyon, Rebecca, Fisher, Michael, Martin, Karen, Eberhart, Izabela, Woods, Christie, Ewings, Sean, Hale, Colin, Rajoli, Rajith K. R., Else, Laura, Dilly‐Penchala, Sujan, Amara, Alieu, Lalloo, David G., Jacobs, Michael, Pertinez, Henry, Hatchard, Parys, Waugh, Robert, and Lawrence, Megan

Subjects
CORONAVIRUS disease treatment, COVID-19, SARS-CoV-2, VOLUNTEERS, VOLUNTEER service, ANTIPARASITIC agents
Abstract

Repurposing approved drugs may rapidly establish effective interventions during a public health crisis. This has yielded immunomodulatory treatments for severe coronavirus disease 2019 (COVID‐19), but repurposed antivirals have not been successful to date because of redundancy of the target in vivo or suboptimal exposures at studied doses. Nitazoxanide is a US Food and Drug Administration (FDA) approved antiparasitic medicine, that physiologically‐based pharmacokinetic (PBPK) modeling has indicated may provide antiviral concentrations across the dosing interval, when repurposed at higher than approved doses. Within the AGILE trial platform (NCT04746183) an open label, adaptive, phase I trial in healthy adult participants was undertaken with high‐dose nitazoxanide. Participants received 1,500 mg nitazoxanide orally twice‐daily with food for 7 days. Primary outcomes were safety, tolerability, optimum dose, and schedule. Intensive pharmacokinetic (PK) sampling was undertaken day 1 and 5 with minimum concentration (Cmin) sampling on days 3 and 7. Fourteen healthy participants were enrolled between February 18 and May 11, 2021. All 14 doses were completed by 10 of 14 participants. Nitazoxanide was safe and with no significant adverse events. Moderate gastrointestinal disturbance (loose stools or diarrhea) occurred in 8 participants (57.1%), with urine and sclera discoloration in 12 (85.7%) and 9 (64.3%) participants, respectively, without clinically significant bilirubin elevation. This was self‐limiting and resolved upon drug discontinuation. PBPK predictions were confirmed on day 1 but with underprediction at day 5. Median Cmin was above the in vitro target concentration on the first dose and maintained throughout. Nitazoxanide administered at 1,500 mg b.i.d. with food was safe with acceptable tolerability a phase Ib/IIa study is now being initiated in patients with COVID‐19. [ABSTRACT FROM AUTHOR]

Published
2022
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22. Strontium isotope dynamics reveal streamflow contributions from shallow flow paths during snowmelt in a montane watershed, Provo River, Utah, USA.

Author

Hale, Colin A., Carling, Gregory T., Nelson, Stephen T., Fernandez, Diego P., Brooks, Paul D., Rey, Kevin A., Tingey, David G., Packer, Brian N., and Aanderud, Zachary T.

Subjects
STRONTIUM isotopes, SNOWMELT, STREAMFLOW, STREAM chemistry, WATER chemistry, DUST
Abstract

Quantifying the routing of snowmelt to surface water is critical for predicting the impacts of atmospheric deposition and changing land use on water quality in montane catchments. To investigate solute sources and streamflow in the montane Provo River watershed (Utah, USA), we used time‐series 87Sr/86Sr ratios sampled at three sites (Soapstone, Woodland and Hailstone) across a gradient of bedrock types. Soils are influenced by aeolian dust contributions, with distinct 87Sr/86Sr ratios relative to siliciclastic bedrock, providing an opportunity to investigate shallow versus deeper flow paths for controlling water chemistry. At the most upstream site (Soapstone), Sr concentrations averaged ~17 μg/L with minimal dilution during snowmelt suggesting subsurface flow paths dominated streamflow. However, a decrease in 87Sr/86Sr ratios from ~0.717 during baseflow to as low as ~0.713 during snowmelt indicated the activation of shallow flow paths through dust‐derived soils. In contrast, downstream sites receiving water inputs from Sr‐rich carbonate bedrock (Woodland and Hailstone) exhibited strong dilution of Sr from ~120 to 20 μg/L and an increase in 87Sr/86Sr ratios from ~0.7095 to ~0.712 during snowmelt. A three‐component mixing model using 87Sr/86Sr ratios and Sr concentrations at Soapstone showed water inputs were dominated by direct snowmelt and flushed soil water during runoff and groundwater during baseflow. At Woodland and Hailstone, a two‐component mixing model showed that the river was a mixture of groundwater and up to 75% upstream channel water during snowmelt. Our findings highlight the importance of flushed soil water for controlling stream water discharge and chemistry during snowmelt, with the signal from the upstream site propagating downstream in a nested catchment. Further, aeolian dust contributes to the solute chemistry of montane streams with potential impacts on water quality along shallow flow paths. Potential contaminants in these surface soils (e.g., Pb deposition in dust) may have significant impacts on water quality during snowmelt runoff. [ABSTRACT FROM AUTHOR]

Published
2022
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24. Are the kids alright? Exploring students' experiences of support mechanisms to enhance wellbeing on an engineering programme in the UK.

Author

Chadha, Deesha, Kogelbauer, Andreas, Campbell, James, Hellgardt, Klaus, Maraj, Marsha, Shah, Umang, Brechtelsbauer, Clemens, and Hale, Colin

Subjects
WELL-being, ENGINEERING students, TUTORS & tutoring, STUDENT well-being
Abstract

In this paper, we aim to explore students' experiences of support mechanisms that support their wellbeing on an engineering degree programme at a research-intensive higher education institution and understand how theory relates to practice. This study was conducted using a mixed-methods approach involving student survey responses (N = 173), interviews with 16 students and focus groups. Kahu and Nelson's conceptual framework was used as a lens through which to explore student support mechanisms. Preliminary data analysis indicates that the intense workload adversely affects students as do some of the interactions they have with personal tutors and their peers. Our findings suggest that workload needs to be reduced, personal tutors need to fill gaps in their skills set, especially associated with student support, and institutional and departmental protocols be continually updated to support student wellbeing. Additionally, student wellbeing officers and professional, dedicated wellbeing advisors could be part of a long-term solution. [ABSTRACT FROM AUTHOR]

Published
2021
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26. Teaming with Confidence: How Peer Connections in Problem-based Learning Impact the Team and Academic Self-efficacy of Engineering Students.

Author

Maraj, Marsha, Hale, Colin Paul, Kogelbauer, Andreas, and Hellgardt, Klaus

Abstract

Engineers will routinely work in teams to solve complex problems. Team-working and collaboration are therefore an integral part of engineering education as they offer enhanced opportunities of acquiring both transferable and subject-specific skills. This paper examines the experiences of third-year engineering students studying a designbased module which uses problem-based learning (PBL) as the main pedagogical approach where students work in teams of 5 or 6 to achieve the associated learning outcomes. PBL allows students to not only play an active role in their own learning but also affords the added opportunity of learning with and from each other (peer learning). The success of this experience can however, be impacted by the team efficacy which exists or ensues as part of the process. These interactions can influence academic self-efficacy and a key aim of this paper is to use the students' perceptions of their experiences with PBL to examine the relationships which exist among academic self-efficacy, peer learning and team efficacy within the module. Findings show that a large percentage of students (85%) felt they learned from each other and that this collaborative experience strongly improved their understanding of mechanical design principles. Self-efficacy scales ranging from 0 (cannot do at all) to 100 (highly certain can do) showed that 65% of students rated their average academic self-efficacy across all learning outcomes as high (above 75). This efficacy was positively related to the support received from peers. Only 6% of respondents indicated that they would be confident undertaking the module by themselves and that while peer-to-peer interactions helped with sharing the workload and producing deliverables, they would have been able to successfully tackle the module alone had the time allotted been increased proportionally. This information is valuable as it can inform and direct future module design within our programme in which many modules are team-based. This could involve and lead to the introduction of new- and the strengthening of existing peer learning opportunities which could transform the way we teach and learn in our department. [ABSTRACT FROM AUTHOR]

Published
2019

30. Molnupiravir versus placebo in unvaccinated and vaccinated patients with early SARS-CoV-2 infection in the UK (AGILE CST-2): a randomised, placebo-controlled, double-blind, phase 2 trial.

Author

Khoo, Saye H, FitzGerald, Richard, Saunders, Geoffrey, Middleton, Calley, Ahmad, Shazaad, Edwards, Christopher J, Hadjiyiannakis, Dennis, Walker, Lauren, Lyon, Rebecca, Shaw, Victoria, Mozgunov, Pavel, Periselneris, Jimstan, Woods, Christie, Bullock, Katie, Hale, Colin, Reynolds, Helen, Downs, Nichola, Ewings, Sean, Buadi, Amanda, and Cameron, David

Subjects
*MOLNUPIRAVIR, *COVID-19, *VACCINATION status, *PROPORTIONAL hazards models, *VACCINATION
Abstract

Background: The antiviral drug molnupiravir was licensed for treating at-risk patients with COVID-19 on the basis of data from unvaccinated adults. We aimed to evaluate the safety and virological efficacy of molnupiravir in vaccinated and unvaccinated individuals with COVID-19.Methods: This randomised, placebo-controlled, double-blind, phase 2 trial (AGILE CST-2) was done at five National Institute for Health and Care Research sites in the UK. Eligible participants were adult (aged ≥18 years) outpatients with PCR-confirmed, mild-to-moderate SARS-CoV-2 infection who were within 5 days of symptom onset. Using permuted blocks (block size 2 or 4) and stratifying by site, participants were randomly assigned (1:1) to receive either molnupiravir (orally; 800 mg twice daily for 5 days) plus standard of care or matching placebo plus standard of care. The primary outcome was the time from randomisation to SARS-CoV-2 PCR negativity on nasopharyngeal swabs and was analysed by use of a Bayesian Cox proportional hazards model for estimating the probability of a superior virological response (hazard ratio [HR]>1) for molnupiravir versus placebo. Our primary model used a two-point prior based on equal prior probabilities (50%) that the HR was 1·0 or 1·5. We defined a priori that if the probability of a HR of more than 1 was more than 80% molnupiravir would be recommended for further testing. The primary outcome was analysed in the intention-to-treat population and safety was analysed in the safety population, comprising participants who had received at least one dose of allocated treatment. This trial is registered in ClinicalTrials.gov, NCT04746183, and the ISRCTN registry, ISRCTN27106947, and is ongoing.Findings: Between Nov 18, 2020, and March 16, 2022, 1723 patients were assessed for eligibility, of whom 180 were randomly assigned to receive either molnupiravir (n=90) or placebo (n=90) and were included in the intention-to-treat analysis. 103 (57%) of 180 participants were female and 77 (43%) were male and 90 (50%) participants had received at least one dose of a COVID-19 vaccine. SARS-CoV-2 infections with the delta (B.1.617.2; 72 [40%] of 180), alpha (B.1.1.7; 37 [21%]), omicron (B.1.1.529; 38 [21%]), and EU1 (B.1.177; 28 [16%]) variants were represented. All 180 participants received at least one dose of treatment and four participants discontinued the study (one in the molnupiravir group and three in the placebo group). Participants in the molnupiravir group had a faster median time from randomisation to negative PCR (8 days [95% CI 8-9]) than participants in the placebo group (11 days [10-11]; HR 1·30, 95% credible interval 0·92-1·71; log-rank p=0·074). The probability of molnupiravir being superior to placebo (HR>1) was 75·4%, which was less than our threshold of 80%. 73 (81%) of 90 participants in the molnupiravir group and 68 (76%) of 90 participants in the placebo group had at least one adverse event by day 29. One participant in the molnupiravir group and three participants in the placebo group had an adverse event of a Common Terminology Criteria for Adverse Events grade 3 or higher severity. No participants died (due to any cause) during the trial.Interpretation: We found molnupiravir to be well tolerated and, although our predefined threshold was not reached, we observed some evidence that molnupiravir has antiviral activity in vaccinated and unvaccinated individuals infected with a broad range of SARS-CoV-2 variants, although this evidence is not conclusive.Funding: Ridgeback Biotherapeutics, the UK National Institute for Health and Care Research, the Medical Research Council, and the Wellcome Trust. [ABSTRACT FROM AUTHOR]

Published
2023
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31. Quantum ghost imaging through turbulence.

Author

Dixon, P. Ben, Howland, Gregory A., Chan, Kam Wai Clifford, O'Sullivan-Hale, Colin, Rodenburg, Brandon, Hardy, Nicholas D., Shapiro, Jeffrey H., Simon, D. S., Sergienko, A. V., Boyd, R. W., and Howell, John C.

Subjects
*TURBULENCE, *PHOTONS, *FLUID dynamics, *QUANTUM theory, *BOUNDARY layer noise
Abstract

We investigate the effect of turbulence on quantum ghost imaging. We use entangled photons and demonstrate that for a specific experimental configuration the effect of turbulence can be greatly diminished. By decoupling the entangled photon source from the ghost-imaging central image plane, we are able to dramatically increase the ghost-image quality. When imaging a test pattern through turbulence, this method increases the imaged pattern visibility from V=0.15±0.04 to 0.42±0.04. [ABSTRACT FROM AUTHOR]

Published
2011
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32. Optimal dose and safety of molnupiravir in patients with early SARS-CoV-2: a Phase I, open-label, dose-escalating, randomized controlled study.

Author

Khoo SH, Fitzgerald R, Fletcher T, Ewings S, Jaki T, Lyon R, Downs N, Walker L, Tansley-Hancock O, Greenhalf W, Woods C, Reynolds H, Marwood E, Mozgunov P, Adams E, Bullock K, Holman W, Bula MD, Gibney JL, Saunders G, Corkhill A, Hale C, Thorne K, Chiong J, Condie S, Pertinez H, Painter W, Wrixon E, Johnson L, Yeats S, Mallard K, Radford M, Fines K, Shaw V, Owen A, Lalloo DG, Jacobs M, and Griffiths G

Subjects
Adult, Bayes Theorem, Humans, Research Design, Treatment Outcome, COVID-19, SARS-CoV-2
Abstract

Objectives: AGILE is a Phase Ib/IIa platform for rapidly evaluating COVID-19 treatments. In this trial (NCT04746183) we evaluated the safety and optimal dose of molnupiravir in participants with early symptomatic infection., Methods: We undertook a dose-escalating, open-label, randomized-controlled (standard-of-care) Bayesian adaptive Phase I trial at the Royal Liverpool and Broadgreen Clinical Research Facility. Participants (adult outpatients with PCR-confirmed SARS-CoV-2 infection within 5 days of symptom onset) were randomized 2:1 in groups of 6 participants to 300, 600 and 800 mg doses of molnupiravir orally, twice daily for 5 days or control. A dose was judged unsafe if the probability of 30% or greater dose-limiting toxicity (the primary outcome) over controls was 25% or greater. Secondary outcomes included safety, clinical progression, pharmacokinetics and virological responses., Results: Of 103 participants screened, 18 participants were enrolled between 17 July and 30 October 2020. Molnupiravir was well tolerated at 300, 600 and 800 mg doses with no serious or severe adverse events. Overall, 4 of 4 (100%), 4 of 4 (100%) and 1 of 4 (25%) of the participants receiving 300, 600 and 800 mg molnupiravir, respectively, and 5 of 6 (83%) controls, had at least one adverse event, all of which were mild (≤grade 2). The probability of ≥30% excess toxicity over controls at 800 mg was estimated at 0.9%., Conclusions: Molnupiravir was safe and well tolerated; a dose of 800 mg twice daily for 5 days was recommended for Phase II evaluation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2021
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